FDA Seeks Comments on 18 New Tobacco HPHC Additions

Content

ACTION:

Notice; established list additions and request for comments.

SUMMARY:

The Food and Drug Administration (FDA, the Agency, or we) is adding constituents to the list of harmful and potentially harmful
constituents (HPHCs) in tobacco products and tobacco smoke (the established HPHC list) as required by the Federal Food, Drug,
and Cosmetic Act (the FD&C Act).

DATES:

Either electronic or written comments on the notice must be submitted by May 26, 2026.

ADDRESSES:

You may submit comments as follows. Please note that late, untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until

11:59 p.m. Eastern Time at the end of May 26, 2026. Comments received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are received on or before that date.

Electronic Submissions

Submit electronic comments in the following way:

• Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring
that your comment does not include any confidential information that you or a third party may not wish to be posted, such
as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing
process. Please note that if you include your name, contact information, or other information that identifies you in the body
of your comments, that information will be posted on https://www.regulations.gov.

• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see “Written/Paper Submissions” and “Instructions”).

Written/Paper Submissions

Submit written/paper submissions as follows:

• Mail/Hand Delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

• For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in “Instructions.” Instructions: All submissions received must include the Docket No. FDA-2026-N-2642 for “Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke; Established List Additions and Request for Comments.” Received comments, those filed in a timely manner (see ADDRESSES ), will be placed in the docket and, except for those submitted as “Confidential Submissions,” publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.

• Confidential Submissions—To submit a comment with confidential information that you do not wish to be made publicly available,
submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states “THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.” The
Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second
copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and
posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly
available, you can provide this information on the cover sheet and not in the body of your comments and you must identify
this information as “confidential.” Any information marked as “confidential” will not be disclosed except in accordance with
21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets,
see 80 FR 56469, September 18, 2015, or access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.

Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the “Search” box and follow the prompts
and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500.

FOR FURTHER INFORMATION CONTACT:

Anna Julia Adams or Matthew Brenner, Center for Tobacco Products, Food and Drug Administration, Document Control Center, Bldg.
71, Rm. G335, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002; 1-877-287-1373, CTPRegulations@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Introduction

The Family Smoking Prevention and Tobacco Control Act (Pub. L. 111-31), enacted on June 22, 2009, amended the FD&C Act by,
among other things, adding a new chapter (chapter IX) granting FDA the authority to regulate the manufacture, marketing, and
distribution of tobacco products to protect the public health. Cigarettes, cigarette tobacco, roll-your-own (RYO) tobacco,
and smokeless tobacco were immediately subject to chapter IX.

For other types of tobacco products, the statute authorizes FDA to issue regulations “deeming” them to be subject to chapter
IX. FDA published a final rule on May 10, 2016, deeming all products that meet the statutory definition of “tobacco product”
set forth in section 201(rr) of the FD&C Act (21 U.S.C. 321(rr)), including components and parts, but excluding accessories
of deemed products, to be subject to chapter IX of the FD&C Act. (1)

Section 904(e) of the FD&C Act (21 U.S.C. 387d(e)) requires FDA to establish, and periodically revise as appropriate, “a list
of harmful and potentially harmful constituents, including smoke constituents, to health in each tobacco product by brand
and by quantity in each brand and subbrand.”

In 2011, FDA provided guidance that discussed the meaning of “harmful and potentially harmful constituent” in the context
of the HPHC list requirement (76 FR 5387, January 31, 2011). (2) In 2012, after considering comments solicited from the public, as well as scientific and other information, FDA developed
a list of 93 constituents in tobacco products and tobacco smoke that are believed to be harmful or potentially harmful to
health (the HPHC established list). (3)

In August 2016, FDA extended its authority under the Deeming Rule to all products, including components and parts (but excluding
accessories of deemed products) that met the statutory definition of tobacco product, including electronic nicotine delivery
systems (ENDS). Therefore, consistent with section 904(e) of the FD&C Act, the Agency considered revising the HPHC established
list to reflect the current range of tobacco products now subject to the Agency's tobacco product

authorities as well as the Agency's growing scientific expertise with respect to all tobacco products. In 2019, the Agency
requested comments on whether 19 additional constituents should be added to the HPHC established list. The Agency has considered
comments solicited from the public, as well as scientific and other information, and has added tobacco product constituents
to the established HPHC list that FDA currently believes are harmful or potentially harmful to health based on scientific
evidence. FDA is adding 18 new constituents to the established list consistent with the requirement in section 904(e) of the
FD&C Act to periodically revise, as appropriate, the established HPHC list (Table 1). In this document, we are also finalizing
the addition of a new criterion for whether a constituent should be added to the list and seeking comments on the proposed
addition of three new constituents to the list.

II. Background

FDA first established the HPHC list on April 3, 2012 (77 FR 20034) (the April 2012 notice). (4) The list currently contains 93 HPHCs. The April 2012 notice describes the history of the HPHC established list, and for additional
background, we refer readers to that notice and the notice FDA published in the
Federal Register
on August 12, 2011 (76 FR 50226) (the August 2011 notice), in which we solicited public comment, including scientific and
other information, concerning the HPHCs in tobacco products and tobacco smoke, such as constituents that should be included
on the HPHC established list, and the criteria used in determining whether a constituent is harmful or potentially harmful
such that it should be included on the HPHC list. (5)

Further, on August 5, 2019 (84 FR 38032) (the August 2019 notice), FDA published a request for comments on 19 additional constituents
proposed to be added to the established list to reflect the current range of tobacco products subject to the Agency's tobacco
product authorities as well as the Agency's growing scientific expertise with respect to all tobacco products. The August
2019 notice mentions FDA's application of existing criteria to deemed tobacco products to propose the addition of glycidol
and ethylene glycol. Glycidol is a thermal byproduct of glycerol and a common component in e-liquids. Ethylene glycol, which
has also been identified in e-liquids, adversely affects reproduction and development. The notice also stated that FDA would
tentatively apply one additional criterion regarding whether a constituent should be included on the HPHC list: constituents
identified by the National Institute for Occupational Safety and Health (NIOSH) as having adverse respiratory effects. The
notice also proposed diethylene glycol (DEG) be added to the list due to it being a potential contaminant in either glycerol
or propylene glycol. If ingested, DEG can cause kidney failure, neurological damage, and death.

When determining whether a constituent should be included on the established HPHC list, FDA considers whether there is evidence
that the constituent meets established criteria, such as determinations from third-party scientific and public health organizations
like NIOSH, the Environmental Protection Agency (EPA) or the Agency for Toxic Substances and Disease Registry (ATSDR). As
part of the Centers for Disease Control and Prevention, NIOSH is the Federal agency responsible for conducting research and
making science-based recommendations to prevent work-related illness and injuries, including those related to human health
hazards and respiratory disease from inhalation exposures to toxicants. FDA has now finalized its previously tentative conclusion
that constituents identified by NIOSH as respiratory toxicants will be an additional criterion that will be applied for determining
whether a constituent should be included on the HPHC established list. The previously established criteria for determining
whether a constituent should be included on the established HPHC list includes constituents identified by the EPA or ATSDR
as having adverse respiratory or cardiac effects. Considering information from NIOSH in this regard is consistent with FDA's
current practice of looking to other recognized, government experts such as EPA or ATSDR for their ability to identify constituents
as having adverse respiratory or cardiac effects. As indicated by the original criteria (the April 2012 notice), FDA has previously
considered this information from NIOSH when determining whether a constituent is harmful or potentially harmful by including
constituents identified by NIOSH as a potential occupational carcinogen as a current criterion.

After review and consideration of the relevant comments received from the August 2019 notice, FDA is adding 18 of the 19 proposed
constituents to the HPHC list. Although FDA proposed that ethyl acetoacetate be added to the list, based on it having been
tentatively identified as a respiratory toxicant, FDA has determined that there is insufficient information to warrant its
inclusion on the list at this time. FDA's determination is based on the fact that ethyl acetoacetate does not meet any of
the criteria for adding constituents to the HPHC list, including that NIOSH has not identified it as having adverse respiratory
effects. This determination may be revised, consistent with the directive in section 904(e) of the FD&C Act that FDA periodically
revise the established list as appropriate. The list of the constituents added to the established HPHC list is in Table 1. (6)

| Constituent | Carcinogen (CA), respiratory toxicant (RT), reproductive or developmental
toxicant (RDT), poisonous chemical (PC) |
| --- | --- |
| Acetic Acid | RT |
| Acetoin (also known as 3-hydroxy-2-butanone) | RT |
| Acetyl Propionyl (also known as 2,3-pentanedione) | RT |
| Benzyl Acetate | RT |
| Butyraldehyde | RT |
| Diacetyl | RT |
| Diethylene Glycol | PC |
| Ethyl Acetate | RT |
| Ethylene Glycol | RT, RDT |
| Furfural | RT |
| Glycerol | RT |
| Glycidol | CA |
| Isoamyl Acetate | RT |
| Isobutyl Acetate | RT |
| Methyl Acetate | RT |
| n-Butanol | RT |
| Propionic Acid | RT |
| Propylene Glycol | RT |

III. Request for Comments and Information

Based on the August 2019 notice, FDA received several comments that suggested adding constituents to the established HPHC
list beyond those proposed in the notice. FDA has statutory authority under section 904(e) of the FD&C Act and intends to
continue to revise the established HPHC list as additional criteria are defined and additional scientific information becomes
available. As a result of comments to the August 2019 notice, FDA is proposing to add three additional constituents to the
established list and requests comments on the three proposed additions: pulegone, furfuryl alcohol, and methyl eugenol. These
constituents are often added to e-liquid formulations as flavors, but may also be present in other tobacco products, such
as cigarettes and smokeless tobacco. FDA has tentatively concluded that these three constituents meet the criteria used in
determining whether a constituent is harmful or potentially harmful and should be included on the HPHC established list, unless
other scientific information obtained by or submitted to the Agency shows that the constituent is not, in fact, harmful or
potentially harmful.

IV. Identification of HPHCs Is an Ongoing Effort

FDA continues to review relevant science to determine whether to add additional constituents to the list. That a constituent
has not been so identified by FDA or other entities could be because it does not currently meet established criteria, it has
not been adequately studied, or it has not yet been systematically reviewed. Consistent with the obligations under section
904(e) of the FD&C Act, FDA intends to continue: (1) our efforts to review other disease outcomes to assess whether additional
chemicals or chemical compounds in tobacco products or tobacco smoke, including chemicals or chemical compounds in the emissions
from the range of tobacco products now deemed to be subject to chapter IX of the FD&C Act, are harmful or potentially harmful
constituents that contribute to the risk of other diseases; (2) our consideration of whether additional or different criteria
should be selected to help identify other classes of harmful or potentially harmful chemicals and chemical compounds for inclusion
on the HPHC established list and whether individual constituents should be added; and (3) our efforts to review new information
to determine if it would be appropriate to remove one or more of the constituents that appear on the HPHC established list,
or to add additional constituents to the list.

| Constituent | Carcinogen (CA), respiratory toxicant (RT), cardiovascular toxicant (CT),
reproductive or developmental toxicant (RDT), addictive (AD), poisonouschemical (PC), banned in food(in smokeless tobacco products) |
| --- | --- |
| Acetaldehyde | CA, RT, AD |
| Acetamide | CA |
| Acetic Acid | RT |
| Acetone | RT |
| Acrolein | RT, CT |
| Acrylamide | CA |
| Acrylonitrile | CA, RT |
| Aflatoxin B1 | CA |
| 4-Aminobiphenyl | CA |
| 1-Aminonaphthalene | CA |
| 2-Aminonaphthalene | CA |
| Ammonia | RT |
| Anabasine | AD |
| o-Anisidine | CA |
| Arsenic | CA, CT, RDT |
| A-α-C (2-Amino-9 H -pyrido[2,3- b ]indole) | CA |
| Benz[a ]anthracene | CA, CT |
| Benz[j ]aceanthrylene | CA |
| Benzene | CA, CT, RDT |
| Benzo[b ]fluoranthene | CA, CT |
| Benzo[k ]fluoranthene | CA, CT |
| Benzo[b ]furan | CA |
| Benzo[a ]pyrene | CA |
| Benzo[c ]phenanthrene | CA |
| Benzyl Acetate | RT |
| Beryllium | CA |
| 1,3-Butadiene | CA, RT, RDT |
| Butyraldehyde | RT |
| Cadmium | CA, RT, RDT |
| Caffeic acid | CA |
| Carbon monoxide | RDT |
| Catechol | CA |
| Chlorinated dioxins/furans | CA, RDT |
| Chromium | CA, RT, RDT |
| Chrysene | CA, CT |
| Cobalt | CA, CT |
| Coumarin | Banned in food |
| Cresols (o-, m-, and p-cresol) | CA, RT |
| Crotonaldehyde | CA |
| Cyclopenta[c,d ]pyrene | CA |
| Diacetyl | RT |
| Dibenz[a,h ]anthracene | CA |
| Dibenzo[a,e ]pyrene | CA |
| Dibenzo[a,h ]pyrene | CA |
| Dibenzo[a,i ]pyrene | CA |
| Dibenzo[a,l ]pyrene | CA |
| Diethylene Glycol | PC |
| 2,6-Dimethylaniline | CA |
| Ethyl Acetate | RT |
| Ethyl carbamate (urethane) | CA, RDT |
| Ethylbenzene | CA |
| Ethylene Glycol | RT, RDT |
| Ethylene oxide | CA, RT, RDT |
| Formaldehyde | CA, RT |
| Furan | CA |
| Furfural | RT |
| Glu-P-1 (2-Amino-6-methyldipyrido[1,2- a: 3′,2′- d ]imidazole) | CA |
| Glu-P-2 (2-Aminodipyrido[1,2- a: 3′,2′- d ]imidazole) | CA |
| Glycerol | RT |
| Glycidol | CA |
| Hydrazine | CA, RT |
| Hydrogen cyanide | RT, CT |
| Indeno[1,2,3-cd ]pyrene | CA |
| IQ (2-Amino-3-methylimidazo[4,5- f ]quinoline) | CA |
| Isoamyl Acetate | RT |
| Isobutyl Acetate | RT |
| Isoprene | CA |
| Lead | CA, CT, RDT |
| MeA-α-C (2-Amino-3-methyl)-9 H -pyrido[2,3- b ]indole) | CA |
| Mercury | CA, RDT |
| Methyl Acetate | RT |
| Methyl Ethyl Ketone | RT |
| 5-Methylchrysene | CA |
| 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) | CA |
| Naphthalene | CA, RT |
| n-Butanol | RT |
| Nickel | CA, RT |
| Nicotine | RDT, AD |
| Nitrobenzene | CA, RT, RDT |
| Nitromethane | CA |
| 2-Nitropropane | CA |
| N -Nitrosodiethanolamine (NDELA) | CA |
| N -Nitrosodiethylamine | CA |
| N -Nitrosodimethylamine (NDMA) | CA |
| N -Nitrosomethylethylamine | CA |
| N -Nitrosomorpholine (NMOR) | CA |
| N -Nitrosonornicotine (NNN) | CA |
| N -Nitrosopiperidine (NPIP) | CA |
| N -Nitrosopyrrolidine (NPYR) | CA |
| N -Nitrososarcosine (NSAR) | CA |
| Nornicotine | AD |
| Phenol | RT, CT |
| PhIP (2-Amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine) | CA |
| Polonium-210 | CA |
| Propionic Acid | RT |
| Propionaldehyde | RT, CT |
| Propylene Glycol | RT |
| Propylene oxide | CA, RT |
| Quinoline | CA |
| Selenium | RT |
| Styrene | CA |
| o-Toluidine | CA |
| Toluene | RT, RDT |
| Trp-P-1 (3-Amino-1,4-dimethyl-5 H -pyrido[4,3- b ]indole) | CA |
| Trp-P-2 (1-Methyl-3-amino-5 H -pyrido[4,3- b ]indole ) | CA |
| Uranium-235 | CA, RT |
| Uranium-238 | CA, RT |
| Vinyl acetate | CA, RT |
| Vinyl chloride | CA |
Grace R. Graham, Deputy Commissioner for Policy, Legislation, and International Affairs. [FR Doc. 2026-07910 Filed 4-22-26; 8:45 am] BILLING CODE 4164-01-P

Footnotes

(1) See “Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention
and Tobacco Control Act,” 81 FR 28974 (May 10, 2016), codified at 21 CFR part 1100. On August 9, 2023, the U.S. District Court
for the District of Columbia issued an order vacating FDA's rule deeming tobacco products to be subject to FDA's tobacco product
authorities “insofar as it applies to premium cigars.” Cigar Ass'n of Am. v. FDA, No. 16-cv-01460, 2023 WL 5094869, at *6 (D.D.C. Aug. 9, 2023), affirmed in part, reversed in part, and remanded, 132 F.4th
535 (D.C. Cir. 2025).

(2) FDA revised the 2011 Guidance that discusses the meaning of HPHC in the context of the HPHC list requirement in August 2016.
“Harmful and Potentially Harmful Constituents” in Tobacco Products as Used in Section 904(e) of the Federal Food, Drug, and
Cosmetic Act available at https://www.fda.gov/media/80109/download.

(3) “Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke; Established List,” 77 FR 20034 (April
3, 2012).

(4) “Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke; Established List,” 77 FR 20034 (April
3, 2012).

(5) “Harmful and Potentially Harmful Constituents in Tobacco Products and Tobacco Smoke; Request for Comments,” 76 FR 50226 (August
12, 2011).

(6) See Appendix A for complete HPHC established list.

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